Elucidating the Pathophysiology of Osteoporosis Model Mice Using Novel Molecules Targeting Membrane Transport Systems

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K17004
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57010:Oral biological science-related
• Research Institution: Nagasaki University
• Principal Investigator: YAMAGUCHI Yu 長崎大学, 医歯薬学総合研究科(歯学系), 助教 (50823308)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: Rab44 / Rab GTPase / 破骨細胞 / Rab44ノックアウトマウス / 骨粗鬆症

Outline of Final Research Achievements

The purpose of this study is to elucidate the function of Rab44, focusing on its role in membrane transport. It was found that Rab44 interacts with the actin-binding protein Coronin1C only in its wild-type and GDP-bound forms. The GTP-bound form was shown to inhibit osteoclast differentiation, while the GDP-bound form promoted it. In vitro experiments confirmed that Coronin1C regulates osteoclast formation and controls the motility and migration ability of macrophage-like cells. In vivo experiments also demonstrated that Coronin1C affects osteoclast formation. These findings suggest that Coronin1C binds to the GDP-bound form of Rab44 and regulates osteoclast formation by modulating the cell motility of macrophages.

Free Research Field

常態口腔学

Academic Significance and Societal Importance of the Research Achievements

本研究は、Rab44の膜輸送に関する新しい機能を解明し、特に破骨細胞の形成における役割を明らかにした。Rab44とアクチン結合タンパク質Coronin1Cとの相互作用による破骨細胞形成の新しい調節機構が見出された。さらに、Coronin1Cがマクロファージの運動能と遊走能を調節し、破骨細胞形成に影響を及ぼすことが明らかになった。この知見は、骨粗鬆症などの骨疾患の治療戦略に新しいターゲットを提供する可能性がある。特に、Rab44とCoronin1Cの相互作用を制御することで、破骨細胞の過剰な活性化を抑制し、骨密度の維持や骨量減少の予防に寄与する治療法の開発が期待される。